Opposing effects of Elk-1 multisite phosphorylation shape its response to ERK activation

• DOI: 10.1126/science.aad1872
• Publication Date: 2016-10-13T18:03:01Z
• Authors: Anastasia Mylona; Francois-Xavier T...; Charles Foster; Tammy M. Cheng; Francesc Miralles; Paul A. Bates; Philipp Selenko; Richard Treisman
• Keywords: Mediator; Phosphorylation cascade; Limiting

Multisite phosphorylation regulates many transcription factors, including the serum response factor partner Elk-1. Phosphorylation of transcriptional activation domain (TAD) Elk-1 by protein kinase ERK at multiple sites potentiates recruitment Mediator coactivator complex and activation, but roles individual events had remained unclear. Using time-resolved nuclear magnetic resonance spectroscopy, we found that ERK2 proceeds markedly different rates eight TAD in vitro, which classified as fast, intermediate, slow. Mutagenesis experiments showed fast intermediate promoted interaction whereas modification slow counteracted both functions, thereby limiting output. Progressive thus ensures a self-limiting to occurs independently antagonizing phosphatase activity.